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The insulin-like growth factor 2 receptor (IGF2R) is essential for prenatal growth regulation and shows gene dosage effects on fetal weight that can be affected by  in-vitro  embryo culture. Imprinted maternal expression of murine  Igf2r  is well documented for all fetal tissues excluding brain, but polymorphic imprinting and biallelic expression were reported for  IGF2R  in human. These differences have been attributed to evolutionary changes correlated with specific reproductive strategies. However, data from species suitable for testing this hypothesis are lacking. The domestic cow ( Bos taurus)  carries a single conceptus with a similar gestation length as human. We identified 12 heterozygous concepti informative for imprinting studies among 68  Bos taurus  fetuses at Day 80 of gestation (28% term) and found predominantly maternal  IGF2R  expression in all fetal tissues but brain, which escapes imprinting. Inter-individual variation in allelic expression bias, i.e. expression of the repressed paternal allele relative to the maternal allele, ranged from 4.6−8.9% in heart, 4.3−10.2% in kidney, 6.1−11.2% in liver, 4.6−15.8% in lung and 3.2−12.2% in skeletal muscle. Allelic bias for mesodermal tissues (heart, skeletal muscle) differed significantly ( P <0.05) from endodermal tissues (liver, lung). The placenta showed partial imprinting with allelic bias of 22.9−34.7% and differed significantly ( P <0.001) from all other tissues. Four informative fetuses were generated by  in-vitro  fertilization (IVF) with embryo culture and two individuals displayed fetal overgrowth. However, there was no evidence for changes in imprinting or DNA methylation after IVF, or correlations between allelic bias and fetal weight. In conclusion, imprinting of  Bos taurus IGF2R  is similar to mouse except in placenta, which could indicate an effect of reproductive strategy. Common minor inter-individual variation in allelic bias and absence of imprinting abnormalities in IVF fetuses suggest changes in  IGF2R  expression in overgrown fetuses could be modulated through other mechanisms than changes in imprinting.

plos one

Tissue-Specific and Minor Inter-Individual Variation in Imprinting of IGF2R Is a Common Feature of Bos taurus Concepti and Not Correlated with Fetal Weight